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Vol. 11, Issue 9, 3169-3176, September 2000

P2X₇ Receptor and Polykarion Formation

Simonetta Falzoni,^* Paola Chiozzi,^* Davide Ferrari,^* Gary Buell, and Francesco Di Virgilio^*

 ^*Department of Experimental and Diagnostic Medicine, Section of General Pathology, and  Biotechnology Center, University of Ferrara, Ferrara, Italy; and  Serono Pharmaceutical Research Institute, Geneva, Switzerland

Cell fusion is a central phenomenon during the immune response that leads to formation of large elements called multinucleated giant cells (MGCs) of common occurrence at sites of granulomatous inflammation. We have previously reported on the involvement in this event of a novel receptor expressed to high level by mononuclear phagocytes, the purinergic P2X₇ receptor. Herein, we show that blockade of this receptor by a specific monoclonal antibody prevents fusion in vitro. In contrast, cell fusion is stimulated by addition of enzymes that destroy extracellular ATP (i.e., apyrase or hexokinase). Experiments performed with phagocytes selected for high (P2X₇ hyper) or low (P2X₇ hypo) P2X₇ expression show that fusion only occurs between P2X₇ hyper/P2X₇ hyper and not between P2X₇ hyper/P2X₇ hypo or P2X₇ hypo/P2X₇ hypo. During MGCs formation we detected activation of caspase 3, an enzyme that is powerfully stimulated by P2X₇. Finally, we observed that during MGCs formation, the P2X₇ receptor is preferentially localized at sites of cell-to-cell contact. These findings support the hypothesis originally put forward by our group that the P2X₇ receptor participates in multinucleated giant cell formation.

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Author correspondence to: E-mail address: fdv{at}dns.unife.it.

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Molecular Biology of the Cell
Vol. 11, 3169-3176, September 2000
Copyright © 2000 by The American Society for Cell Biology

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